Contemporary research, life science and other analytical and process laboratories must mix liquids and suspensions to activate, chemically combine and promote cellular or molecular interactions. Mixing is a basic operation applied to all forms and manners of engineered material processing including those used in biological, chemical, pharmaceutical, fermentation, agricultural, petrochemical, and cosmetic processes. Micro-liter (less than 1.0 milliliter) to multi-liter volumes must be mixed. Operations on large or small volume samples require precise, repeatable and controlled mixing and heating for accurate and reproducible results.
Stirring and mixing have been identified as a problem because mixing is incomplete and homogeneity is not attained. This causes further processing errors due to sampling in or between concentration layers, which are not indicative of the materials being mixed. The result is random variation in the process operation and variability and waste in the resulting product. Mixing is a fundamental diffusion process. It is not reversible. Stirring is a mechanical process often used to cause mixing. Stirring may be reversible by natural forces such as gravity, or other imposed forces. When used, effective stirring is essential for thorough mixing. Effective stirring requires physical contact between the materials to be mixed which can not be duplicated by agitating, flicking, vortexing, gassing, rocking, shaking or rolling vessels containing materials to be mixed.
Mixing operations in all volumes require complete mixing. Small volumes in particular, require more complete, and controlled mixing to produce accurate and reproducible results or maximum yield without damaging or otherwise artifactually changing the ingredients.
The basis of this problem is that the present methods develop regular, predictable and symmetrical flow patterns within the liquid or materials being mixed. There are regions that are partially mixed or unmixed and there is a concentration related layering of reactants, some of which are over mixed. Further, it is now known that effective mixing can only be achieved if the flow patterns are disrupted or randomly changed. Existing theories and mixing models do not accurately describe mixing processes and limitations.
Methods used to mix volumes of liquids are based on stirring with paddles, rotating impellers, blades, magnetic bars, or by rocking, rolling, shaking, or vortexing the entire container. All of these methods create symmetrical stirring dynamics, but incomplete mixing because the adjacent materials move in a symmetrical way, in unison and move in a manner that does not include all portions of the material to be mixed. Therefore, mixing is incomplete and homogeneity or maximum yields are not attained. The result is uncontrolled variations in the process operation and variability and waste in the resulting product. Current practice uses baffles either mounted on the container wall or suspended into the container, to disrupt these regular mixing patterns. These baffles are minimally effective, causing only regular and symmetrical patterns. Another practice is utilizing variable pitch impellers to change the mixing patterns. This method will modify the pattern, but the pattern remains because the impeller is still rotating on the same axis. Mixing is a fundamental operation in all forms of material processing. Methods used to mix materials are based on standard physical characteristics of the materials to be mixed including volumes, viscosity, Reynolds number, Schmidt number, vessel geometry, and temperature.
FIG. 1A shows a conventional magnetic stirring technique using a motor 110 that rotates a permanent magnet 115, causing stir bar 105 to move at the bottom of container 120. The motor and magnet are normally located below a platform on which the samples to be mixed are placed. The stirring speed (rpm) is often controlled by a potentiometer (not shown) that varies the voltage to the motor 110. As shown in FIG. 1B, the stirring speed is selected by visibly observing the stir bar capture and stirring dynamics (see flow patterns 125) in the container 120. These conventional techniques have only a limited effect in areas of the liquid that are not close to the stir bar, baffles or impeller. Rocking, shaking or rolling moves the liquid in unison, which limits the interaction of the materials, and also has limited mixing in the center, corners and along the walls of a container. FIG. 1C shows a conventional electromagnetic stirring technique by applying an electrical current to coils 130, which generate an electromagnetic field. The stir bar 105 moves in a horizontal, rotating motion at the bottom of container 120 in response to the electromagnetic field.
FIG. 1D shows a conventional motor driven impeller stirring technique using a motor 110 that rotates an impeller 150 via rotating shaft 145 to mix a liquid material in container 120. This method has inherent contamination disadvantages due to the proximity of the motor, seals and bearings that are associated with the shaft along with cleaning difficulties of all of the components.
Mixing with typical symmetrical patterns and lack of mixing in some areas causes the liquids, or liquids and solids, to move about the container relative to one another, rather than colliding with or diffusing into each other. These methods do not cause the required total exposure and frequent collision with the components being mixed. It is known that symmetrical mixing patterns do not involve the entire volume of the container and do not produce efficient or complete mixing regardless of the length of time mixed. A number of concentration layers exist, which demonstrate the inability of these methods to reach a homogenous state. It has also been demonstrated that turbulent currents and chaotic stirring dynamics enhance the mixing and are essential to attain homogeneity or complete interaction between the materials being mixed. The turbulent element disrupts these patterns and provides enhanced collision and exposure of the components being mixed. It is also known that a stirring device must involve the entire volume to produce effective mixing.
Conventionally positioned horizontal stir bars or impellers can only vary speed, geometry or stirring time and have limited effect in areas of the liquid that are not close to the stir bar or impeller. Rocking, shaking or rolling moves the liquid in unison, limits the interaction of the materials, and also there is limited mixing in corners and along the walls of the container, and near the meniscus or upper most portion of the liquid. These methods rely on high stirring speeds to improve the mixing in areas away from the stirring device, stir bar or impeller. The increased mechanical forces, such as shear, vortexing and cavitations, cause cellular or other fragile components in the liquid or sample to be altered, activated or physically compromised. This is especially important when stirring plant or animal cells, other organisms such as bacteria or viral specimens and proteins, labile molecules or long chain chemicals.
What is needed is an efficient, gentle mixing technique that produces effectively mixed liquids in a container by producing asymmetrical mixing patterns that involve the entire volume of the container without changing of constituents.